The importance of sonographer experience and machine quality with regards to the role of musculoskeletal ultrasound in routine care of rheumatoid arthritis patients.

OBJECTIVES: Regarding recent progress, musculoskeletal ultrasound (US) will probably soon be integrated in standard care of patient with rheumatoid arthritis (RA). However, in daily care, quality of US machines and level of experience of sonographers are varied. We conducted a study to assess reproducibility and feasibility of an US scoring for RA, including US devices of different quality and rheumatologist with various levels of expertise in US as it would be in daily care. METHODS: The Swiss Sonography in Arthritis and Rheumatism (SONAR) group has developed a semi-quantitative score using OMERACT criteria for synovitis and erosion in RA. The score was taught to 108 rheumatologists trained in US. One year after the last workshop, 19 rheumatologists participated in the study. Scans were performed on 6 US machines ranging from low to high quality, each with a different patient. Weighted kappa was calculated for each pair of readers. RESULTS: Overall, the agreement was fair to moderate. Quality of device, experience of the sonographers and practice of the score before the study improved substantially the agreement. Agreement assessed on higher quality machine, among sonographers with good experience in US increased to substantial (median kappa for B-mode and Doppler: 0.64 and 0.41 for erosion). CONCLUSIONS: This study demonstrated feasibility and reproducibility of the Swiss US SONAR score for RA. Our results confirmed importance of the quality of US machine and the training of sonographers for the implementation of US scoring in the routine daily care of RA.

Adjuvant cisplatin-based combined chemotherapy for lymph node (LN)-positive urothelial carcinoma of the bladder (UCB) after radical cystectomy (RC): a retrospective international study of >1500 patients.

OBJECTIVE: To compare outcomes of patients with lymph node (LN)-positive urothelial carcinoma of the bladder (UCB) treated with or without cisplatin-based combined adjuvant chemotherapy (AC) after radical cystectomy (RC). PATIENTS AND METHODS: We retrospectively analysed 1523 patients with LN-positive UCB, who underwent RC with bilateral pelvic LN dissection. All patients had no evidence of disease after RC. AC was administered within 3 months. Competing-risks models were applied to compare UCB-related mortality. RESULTS: Of the 1523 patients, 874 (57.4%) received AC. The cumulative 1-, 2- and 5-year UCB-related mortality rates for all patients were 16%, 36% and 56%, respectively. Administration of AC was associated with an 18% relative reduction in the risk of UCB-related death (subhazard ratio 0.82, P = 0.005). The absolute reduction in mortality was 3.5% at 5 years. The positive effect of AC was detectable in patients aged ≤70 years, in women, in pT3-4 disease, and in those with a higher LN density and lymphovascular invasion. This study is limited by its retrospective and non-randomised design, selection bias, the absence of central pathological review and lack in standardisation of LN dissection and cisplatin-based protocols. CONCLUSION: AC seems to reduce UCB-related mortality in patients with LN-positive UCB after RC. Younger patients, women and those with high-risk features such as pT3-4 disease, a higher LN density and lymphovascular invasion appear to benefit most. Appropriately powered prospective randomised trials are necessary to confirm these findings.

Complications of systemic juvenile idiopathic arthritis: risk factors and management recommendations.

Systemic juvenile idiopathic arthritis (SJIA) is an inflammatory condition characterized by fever, lymphadenopathy, arthritis, rash and serositis. Systemic inflammation has been associated with dysregulation of the innate immune system, suggesting that SJIA is an autoinflammatory disorder. IL-1 and IL-6 play a major role in the pathogenesis of SJIA, and treatment with IL-1 and IL-6 inhibitors has shown to be highly effective. However, complications of SJIA, including macrophage activation syndrome, limitations in functional outcome by arthritis and long-term damage from chronic inflammation, continue to be a major issue in SJIA patients' care. Translational research leading to a profound understanding of the cytokine crosstalk in SJIA and the identification of risk factors for SJIA complications will help to improve long-term outcome.

Rhumatologie. Rhumatisme psoriasique [Update in psoriatic arthritis treatment].

Psoriatic arthritis is a chronic inflammatory disease. It affects up to 40% of patients suffe- ring from skin psoriasis. Joint involvement is relatively heterogeneous. Some clinical manifestations are similar to those of rheumatoid arthritis, others are close to spondylarthritis manifestations and are therefore considered as part of this entity. Treatment depends on initial presentation (peripheral or axial) but often begins with non-steroidal anti-inflammatory drugs and methotrexate, followed by anti-TNFalpha if needed. New therapeutic op- tions are available or under evaluation, parti- cularly targeting cytokines involved in psoriatic arthritis (IL-12/IL-23 and IL-17).

Adjuvant radiotherapy for gastric carcinoma: 10 years follow-up of 244 cases from a single institution.

BACKGROUND: Postoperative chemoradiotherapy (CRT) of gastric carcinoma improves survival among high- risk patients. This study was undertaken to analyse long-term survival probability and the impact of certain covariates on the survival outcome in affected individuals. MATERIALS AND METHODS: Between January 2000 and December 2005, 244 patients with gastric cancer underwent adjuvant radiotherapy (RT) in our institution. Data were retrieved retrospectively from patient files and analysed with SPSS version 21.0. RESULTS: A total of 244 cases, with a male to female ratio of 2.2:1, were enrolled in the study. The median age of the patients was 52 years (range, 20-78 years). Surgical margin status was positive or close in 72 (33%) out of 220 patients. Postoperative adjuvant RT dose was 46 Gy. Median follow-up was 99 months (range, 79-132 months) and 23 months (range, 2-155 months) for surviving patients and all patients, respectively. Actuarial overall survival (OS) probability for 1-, 3-, 5- and 10-year was 79%, 37%, 24% and 16%, respectively. Actuarial progression free survival (PFS) probability was 69%, 34%, 23% and 16% in the same consecutive order. AJCC Stage I-II disease, subtotal gastrectomy and adjuvant CRT were significantly associated with improved OS and PFS in multivariate analyses. Surgical margin status or lymph node dissection type were not prognostic for survival. CONCLUSIONS: Postoperative CRT should be considered for all patients with high risk of recurrence after gastrectomy. Beside well-known prognostic factors such as stage, lymph node status and concurrent chemotherapy, the type of gastrectomy was an important prognostic factor in our series. With our findings we add to the discussion on the definition of required surgical margin for subtotal gastrectomy. We consider that our observations in gastric cancer patients in our clinic can be useful in the future randomised trials to point the way to improved outcomes.

A prospective evaluation of ultrasound as a diagnostic tool in acute microcrystalline arthritis.

INTRODUCTION: The performance of ultrasound (US) in the diagnosis of acute gouty (MSU) arthritis and calcium pyrophosphate (CPP) arthritis is not yet well defined. Most studies evaluated US as the basis for diagnosing crystal arthritis in already diagnosed cases of gout and few prospective studies have been performed. METHODS: One hundred nine consecutive patients who presented an acute arthritis of suspected microcrystalline arthritis were prospectively included. All underwent an US of the symptomatic joints(s) and of knees, ankles and 1(st) metatarsopalangeal (MTP) joints by a rheumatologist "blinded" to the clinical history. 92 also had standard X-rays. Crystal identification was the gold standard. RESULTS: Fifty-one patients had MSU, 28 CPP and 9 had both crystals by microscopic analysis. No crystals were detected in 21. One had septic arthritis. Based on US signs in the symptomatic joint, the sensitivity of US for both gout and CPP was low (60 % for both). In gout, the presence of US signs in the symptomatic joint was highly predictive of the diagnosis (PPV = 92 %). When US diagnosis was based on an examination of multiple joints, the sensitivity for both gout and CPP rose significantly but the specificity and the PPV decreased. In the absence of US signs in all the joints studied, CPP arthritis was unlikely (NPV = 87 %) particularly in patients with no previous crisis (NPV = 94 %). X-ray of the symptomatic joints was confirmed to be not useful in diagnosing gout and was equally sensitive or specific as US in CPP arthritis. CONCLUSIONS: Arthrocenthesis remains the key investigation for the diagnosis of microcrystalline acute arthritis. Although US can help in the diagnostic process, its diagnostic performance is only moderate. US should not be limited to the symptomatic joint. Examination of multiple joints gives a better diagnostic sensitivity but lower specificity.

The role of adjuvant chemotherapy for lymph node-positive upper tract urothelial carcinoma following radical nephroureterectomy: a retrospective study.

OBJECTIVE: To evaluate the effect of adjuvant chemotherapy (AC) on mortality after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) with positive lymph nodes (LNs) and to identify patient subgroups that are most likely to benefit from AC. PATIENTS AND METHODS: We retrospectively analysed data of 263 patients with LN-positive UTUC, who underwent full surgical resection. In all, 107 patients (41%) received three to six cycles of AC, while 156 (59.3%) were treated with RNU alone. UTUC-related mortality was evaluated using competing-risks regression models. RESULTS: In all patients (Tall N+), administration of AC had no significant impact on UTUC-related mortality on univariable (P = 0.49) and multivariable (P = 0.11) analysis. Further stratified analyses showed that only N+ patients with pT3-4 disease benefited from AC. In this subgroup, AC reduced UTUC-related mortality by 34% (P = 0.019). The absolute difference in mortality was 10% after the first year and increased to 23% after 5 years. On multivariable analysis, administration of AC was associated with significantly reduced UTUC-related mortality (subhazard ratio 0.67, P = 0.022). Limitations of this study are the retrospective non-randomised design, selection bias, absence of a central pathological review and different AC protocols. CONCLUSIONS: AC seems to reduce mortality in patients with pT3-4 LN-positive UTUC after RNU. This subgroup of LN-positive patients could serve as target population for an AC prospective randomised trial.

Clinical utility of a molecular test in adjuvant treatment decision making in women with endocrine-sensitive early stage breast cancer: a retrospective, single center one year experience

Background. Molecular tests for breast cancer (BC) risk assessment are reimbursed by health insurances in Switzerland since the beginning of year 2015. The main current role of these tests is to help oncologists to decide about the usefulness of adjuvant chemotherapy in patients with early stage endocrine-sensitive and human epidermal growth factor receptor 2 (HER2)-negative BC. These gene expression signatures aim at predicting the risk of recurrence in this subgroup. One of them (OncotypeDx/OT) also predicts distant metastases rate with or without the addition of cytotoxic chemotherapy to endocrine therapy. The clinical utility of these tests -in addition to existing so-called "clinico-pathological" prognostic and predictive criteria (e.g. stage, grade, biomarkers status)-is still debated. We report a single center one year experience of the use of one molecular test (OT) in clinical decision making. Methods. We extracted from the CHUV Breast Cancer Center data base the total number of BC cases with estrogen-receptor positive (ER+), HER2-negative early breast cancer (node negative (pN0) disease or micrometastases in up to 3 lymph nodes) operated between September 2014 and August 2015. For the cases from this group in which a molecular test had been decided by the tumor board, we collected the clinicopathologic parameters, the initial tumor board decision, and the final adjuvant systemic therapy decision. Results. A molecular test (OT) was done in 12.2% of patients with ER + HER2 negative early BC. The median age was 57.4 years and the median invasive tumor size was 1.7 cm. These patients were classified by ODX testing (Recurrence Score) into low-, intermediate-, and high risk groups, respectively in 27.2%, 63.6% and 9% of cases. Treatment recommendations changed in 18.2%, predominantly from chemotherapyendocrine therapy to endocrine treatment alone. Of 8 patients originally recommended chemotherapy, 25% were recommended endocrine treatment alone after receiving the Recurrence Score result. Conclusions. Though reimbursed by health insurances since January 2015, molecular tests are used moderately in our institution as per the decision of the multidisciplinary tumor board. It's mainly used to obtain a complementary confirmation supporting the decision of no chemotherapy. The OncotypeDx Recurrence Score results were in the intermediate group in 66% of the 9 tested cases but contributed to avoid chemotherapy in 2 patients during the last 12 months.

The difference of disease perception by juvenile idiopathic arthritis patients and their parents : analysis of the JAMAR questionnaire.

BACKGROUND: The JAMAR (Juvenile Arthritis Multidimensional Assessment Report) has been developed to evaluate the perception of the patient and his parents on different items: well-being, pain, functional status, quality of life, disease activity, disease course, side effects of medication, therapeutic compliance and satisfaction with illness outcome. Our aim was to compare disease's perception by JIA patients and their parents. METHODS: We included into the study 100 consecutive patients over 7 years of age. We asked both parent and child to complete the JAMAR questionnaire. For each patient we recorded demographic and disease related data. We examined the level of disagreement between children and parents for the quantitative items of the JAMAR: VAS Pain, VAS Disease Activity, VAS Well Being, Juvenile Arthritis Functional Score, HRQoL. Then we looked for a relation between discordance-rate and demographic and clinical variables. RESULTS: Children and parents' median scores for all five items were similar. Individual dyads agreement was low, with a large amount of pairs (80) discordant for at least one item. We found higher MD VAS and JADAS in more discordant dyads, suggesting that when the disease is more active discordance between child and parent increase. CONCLUSION: The JAMAR questionnaire is an important tool that helps clinicians to detect divergent child and parent's disease perceptions. It is essential that both patients and parents fill the JAMAR questionnaire for a complete clinical and psychosocial evaluation.

Diagnostic and prognostic value of antibodies against chimeric fibrin/filaggrin citrullinated synthetic peptides in rheumatoid arthritis

Introduction: Evidence suggests that citrullinated fibrin(ogen) may be a potential in vivo target of anticitrullinated protein/peptide antibodies (ACPA) in rheumatoid arthritis (RA). We compared the diagnostic yield of three enzyme-linked immunosorbent assay (ELISA) tests by using chimeric fibrin/filaggrin citrullinated synthetic peptides (CFFCP1, CFFCP2, CFFCP3) with a commercial CCP2-based test in RA and analyzed their prognostic values in early RA. Methods: Samples from 307 blood donors and patients with RA (322), psoriatic arthritis (133), systemic lupus erythematosus (119), and hepatitis C infection (84) were assayed by using CFFCP- and CCP2-based tests. Autoantibodies also were analyzed at baseline and during a 2-year follow-up in 98 early RA patients to determine their prognostic value. Results: With cutoffs giving 98% specificity for RA versus blood donors, the sensitivity was 72.1% for CFFCP1, 78.0% for CFFCP2, 71.4% for CFFCP3, and 73.9% for CCP2, with positive predictive values greater than 97% in all cases. CFFCP sensitivity in RA increased to 80.4% without losing specificity when positivity was considered as any positive anti-CFFCP status. Specificity of the three CFFCP tests versus other rheumatic populations was high (> 90%) and similar to those for the CCP2. In early RA, CFFCP1 best identified patients with a poor radiographic outcome. Radiographic progression was faster in the small subgroup of CCP2-negative and CFFCP1-positive patients than in those negative for both autoantibodies. CFFCP antibodies decreased after 1 year, but without any correlation with changes in disease activity. Conclusions: CFFCP-based assays are highly sensitive and specific for RA. Early RA patients with anti-CFFCP1 antibodies, including CCP2-negative patients, show greater radiographic progression.

Acute Hepatitis E Virus infection with coincident reactivation of Epstein-Barr virus infection in an immunosuppressed patient with rheumatoid arthritis: a case report.

BACKGROUND: Hepatitis E virus (HEV) is the most recently discovered of the hepatotropic viruses, and is considered an emerging pathogen in developed countries with the possibility of fulminant hepatitis in immunocompromised patients. Especially in the latter elevated transaminases should be taken as a clue to consider HEV infection, as it can be treated by discontinuation of immunosuppression and/or ribavirin therapy. To our best knowledge, this is a unique case of autochthonous HEV infection with coincident reactivation of Epstein-Barr virus (EBV) infection in an immunosuppressed patient with rheumatoid arthritis (RA). CASE PRESENTATION: A 68-year-old Swiss woman with RA developed hepatitis initially diagnosed as methotrexate-induced liver injury, but later diagnosed as autochthonous HEV infection accompanied by reactivation of her latent EBV infection. She showed confounding serological results pointing to three hepatotropic viruses (HEV, Hepatitis B virus (HBV) and EBV) that could be resolved by detection of HEV and EBV viraemia. The patient recovered by temporary discontinuation of immunosuppressive therapy. CONCLUSIONS: In immunosuppressed patients with RA and signs of liver injury, HEV infection should be considered, as infection can be treated by discontinuation of immunosuppression. Although anti-HEV-IgM antibody assays can be used as first line virological tools, nucleic acid amplification tests (NAAT) for detection of HEV RNA are recommended--as in our case--if confounding serological results from other hepatotropic viruses are obtained. After discontinuation of immunosuppressive therapy, our patient recovered from both HEV infection and reactivation of latent EBV infection without sequelae.

A cast of shadow on adjuvant radiotherapy for prostate cancer: A critical review based on a methodological perspective.

OBJECTIVE: To perform a critical review focusing on the applicability in clinical daily practice of data from three randomized controlled trials (RCTs): SWOG 8794, EORTC 22911, and ARO/AUO 96-02. METHODS AND MATERIALS: An analytical framework, based on the identified population, interventions, comparators, and outcomes (PICO) was used to refine the search of the evidence from the three large randomized trials regarding the use of radiation therapy after prostatectomy as adjuvant therapy (ART). RESULTS: With regard to the inclusion criteria: (1) POPULATION: in the time since they were designed, in two among three trial (SWOG 8794 and EORTC 22911) patients had a detectable PSA at the time of randomization, thus representing de facto a substantial proportion of patients who eventually received salvage RT (SRT) at non-normalised PSA levels rather than ART. (2) INTERVENTIONS: although all the trials showed the benefit of postoperative ART compared to a wait-and-see approach, the dose herein employed would be now considered inadequate; (3) COMPARATORS: the comparison arm in all the 3 RCTs was an uncontrolled observation arm, where patients who subsequently developed biochemical failure were treated in various ways, with up to half of them receiving SRT at PSA well above 1ng/mL, a level that would be now deemed inappropriate; (4) OUTCOMES: only in one trial (SWOG 8794) ART was found to significantly improve overall survival compared to observation, with a ten-year overall survival rate of 74% vs. 66%, although this might be partly the result of imbalanced risk factors due to competing event risk stratification. CONCLUSIONS: ART has a high level of evidence due to three RCTs with at least 10-year follow-up recording a benefit in biochemical PFS, but its penetrance in present daily clinics should be reconsidered. While the benefit of ART or SRT is eagerly expected from ongoing randomized trials, a dynamic risk-stratified approach should drive the decisions making process.